Development of High capacity adenoviral system emplying Ad-HD and helper of distantly related serotypes

• Grant number: 21/02659-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2021
• End date: June 30, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Rodrigo Esaki Tamura
• Grantee: Nicholas Pietro Agulha Toneto
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated research grant: 19/15619-2 - Development of high capacity adenoviral system expressing antitumoral genes, AP.JP

Abstract

Gene therapy through viral vectors has great potential, and is already being used in clinical protocols in humans. Third-generation adenoviral vectors (high-capacity, gutless, or helper-dependent-HD) are safer than first-generation vectors, but the main concern limitation for their large-scale application is to obtain contamination-free helper virus particles. Adenoviruses of phylogenetically close serotypes have the ability to cross-pack, but more phylogenetically distant viruses do not. Thus we will develop high capacity adenoviral vectors, which can be produced by a helper vector, which is phylogenetically distant and, therefore, unable to be packaged and present as a contaminant in the preparation of Ad-HD. Eliminating contamination by the helper virus has great potential to increase the use of high-capacity Adenoviral vectors. In this Project, an Ad-HD vector will be constructed with a packaging sequence derived from serotype 12 adenovirus, while the helper vector will be derived from serotype 5 adenovirus and we will produce packaging cell lines expressing the specific serotype viral proteins, IVA2, IIIa and L1 52/55k, which will allow the specific packaging of the Ad-HD vector, eliminating the presence of the helper virus. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NATÁLIA MENESES ARAÚJO; ILEANA GABRIELA SANCHEZ RUBIO; NICHOLAS PIETRO AGULHA TONETO; MIRIAN GALLIOTE MORALE; RODRIGO ESAKI TAMURA. The use of adenoviral vectors in gene therapy and vaccine approaches. GENETICS AND MOLECULAR BIOLOGY, v. 45, n. 3, 2022-10-07. (19/15619-2, 20/08271-7, 21/02659-6, 21/03418-2)